**3. SLAM, a receptor of morbillivirus**

The characteristics of SLAM have been extensively studied in humans. SLAM (CD150) is a type I transmembrane protein, and there are many members of the SLAM family including the well-known 2B4 (CD244), Ly-9 (CD229), NTB-A, and CD84 [49]. All of the SLAM family members have an extracellular region composed of a membrane-distal immunoglobulin variable (V) domain and a membrane-proximal immunoglobulin constant-2 (C2) domain, along with a cytoplasmic region bearing multiple tyrosine-based switch motifs (ITSMs) that bind cytoplasmic Src homology-2 (SH2)-containing proteins such as SLAM-associated protein (SAP) [50]. Evidence is accumulating that the interaction between the cytoplasmic region of SLAM and SAP family molecules mediates a switch to positive or negative signaling in immune cells and plays a crucial role in multiple immune regulations [22]. Genes for the SLAM family receptors are located within a ~400-kb cluster on chromosome 1 in humans and mice [51]. This gene location, coupled with the conserved exon-intron structure of SLAM-related genes, implies that they were generated by the sequential duplication of a single ancestral gene. A SLAM family receptor forms a homophilic dimer by weak binding between the V domains and acts as a self-ligand, suggesting that the receptors can trigger homotypic or heterotypic cell–cell interactions [52]. The V domain of SLAM (CD150) also provides an interface for binding with morbilliviruses [53]. The viral H protein has a strong affinity for the V domain of SLAM, which is 400-fold higher than for self-ligand interaction [54]. The interaction between the viral H protein and SLAM V domain is the initial event in infection with morbilliviruses. The results of recent detailed structural studies have suggested that the interaction changes the microenvironment of the interaction zone for the fusion activity of the F protein, although the mechanism of membrane fusion mediated by the F protein is not fully understood [55-58].
